Not Applicable
1. Field of the Invention
The present invention relates to regulating the melanin content of mammalian melanocytes; regulating pigmentation in mammalian skin, hair, wool or fur; restoring pigmentation to grey hair; treating or preventing various skin and proliferative disorders; by administration of various compounds, including alcohols, diols and/or triols and their analogues.
2. Description of Related Art
U.S. Pat. No. 5,352,440 is directed to increasing melanin synthesis in melanocytes and increasing pigmentation by administration of certain diacylglycerol compounds.
U.S. Pat. No. 5,532,001 is directed to increasing pigmentation in mammalian skin via administration of certain DNA fragments.
U.S. Pat. No. 5,554,359 is directed to increasing levels of melanin in melanocytes by administration of lysosomotropic agents.
The present invention provides a method for increasing the melanin content of mammalian melanocytes, which comprises administering to said melanocytes an effective amount of a C3-C50 diol, which may be aliphatic or aromatic, linear, branched, mono-, bi- or polyclicic, saturated or unsaturated, unsubstituted, mono- or polysubstituted.
Another aspect of the present invention concerns a method for increasing or restoring pigmentation in mammalian skin, hair or wool, which comprises administering to said mammal an effective amount of one or more compounds described above.
Another aspect of the present invention concerns a method for treating a skin proliferative disorder or a disorder of keratinization in a mammal, which comprises administering to a mammal in need of such treatment an effective amount of one or more compounds described above.
A further aspect of the present invention concerns a method for preventing a skin proliferative disorder or a disorder of keratinization in a mammal, which comprises administering to a mammal in need of such preventive treatment an effective amount of one or more compounds described above.
An additional aspect of the present invention concerns a method for treating a tumorous or cancerous disorder whereby application of one or more of the compounds described above results in reversal of said disorder by virtue of induction of differentiation of cancerous or tumorous cells to a less- or non-proliferative phenotype. These cancerous or tumorous disorders include, but are not limited to, proliferative disorders of a dermatological nature.
In another aspect, the present invention provides a composition for increasing the melanin content of mammalian melanocytes, which comprises:
a) an effective amount of one or more compounds described above; and
b) a suitable carrier.
In another aspect, the present invention provides a composition for treating a skin proliferative disorder or a disorder of keratinization, which comprises:
a) an effective amount of one or more compounds described above; and
b) a suitable carrier.
In yet another aspect, the present invention provides a composition for preventing a skin proliferative disorder, which comprises:
a) an effective amount of one or more compounds described above; and
b) a suitable carrier.
The present invention additionally provides a method for increasing the melanin content of mammalian melanocytes, which comprises administering to said melanocytes an effective amount of one or more compounds having the following structure: 
wherein
each X is independently selected from a single or double bond; or a group containing from one atom to twenty atoms, at least one of which is carbon, nitrogen, oxygen or sulfur;
each R1 is independently selected from hydrogen; halogen; an acyl or amino acyl group containing from one atom to twenty atoms, at least one of which is carbon, nitrogen, oxygen, or sulfur; or a group containing from one atom to twenty atoms, one of which is carbon, nitrogen, oxygen, or sulfur;
R2 is a linear, branched or unbranched, cyclic, bicyclic or polycyclic group containing from one atom to fifty atoms, at least one of which is carbon, nitrogen, oxygen, or sulfur; and
each R is independently selected from R1; R2; hydroxyl, methyl, hydroxymethyl, xe2x80x94(CH2)nCH3xe2x80x94, xe2x80x94(CH2)nOH, xe2x80x94(CH2)nOR1, xe2x80x94(CH2)nxe2x80x94CH(OH)xe2x80x94CHOH, xe2x80x94(CH2)nxe2x80x94CH(OH)xe2x80x94CH(OH)R1, xe2x80x94(CH2)nxe2x80x94CH(OH)xe2x80x94(CH2)nxe2x80x94CH2(OH), xe2x80x94(CH2)nxe2x80x94CH(OH)xe2x80x94(CH2)nxe2x80x94CH(OH)R1 or xe2x80x94CH2OR1, wherein each n is independently an integer from 0-25;
and pharmaceutically acceptable salts or prodrugs thereof, with the proviso that with reference to the first listed structure only, when the X to which R1 is attached is a single bond and each R is acyl and one of R1 is hydroxymethyl (HOCH2xe2x80x94), then the sum of carbon atoms in R1 is greater than one.
Another aspect of the present invention concerns a method for increasing or restoring pigmentation in mammalian skin, hair or wool, which comprises administering to said mammal an effective amount of one or more compounds depicted above.
Another aspect of the present invention concerns a method for treating a skin proliferative disorder or a disorder of keratinization in a mammal, which comprises administering to a mammal in need of such treatment an effective amount of one or more compounds depicted above.
A further aspect of the present invention concerns a method for preventing a skin proliferative disorder or a disorder of keratinization in a mammal, which comprises administering to a mammal in need of such preventive treatment an effective amount of one or more compounds depicted above.
An additional aspect of the present invention concerns a method for treating a tumorous or cancerous disorder whereby application of one or more of the compounds depicted above results in reversal of said disorder by virtue of induction of differentiation of cancerous or tumorous cells to a less- or non-proliferative phenotype. These cancerous or tumorous disorders include, but are not limited to, proliferative disorders of a dermatological nature.
In another aspect, the present invention provides a composition for increasing the melanin content of mammalian melanocytes, which comprises:
a) an effective amount of one or more compounds depicted above; and
b) a suitable carrier.
In another aspect, the present invention provides a composition for treating a skin proliferative disorder or a disorder of keratinization, which comprises:
a) an effective amount of one or more compounds depicted above; and
b) a suitable carrier.
In yet another aspect, the present invention provides a composition for preventing a skin proliferative disorder, which comprises:
a) an effective amount of one or more compounds depicted above; and
b) a suitable carrier.
In yet another aspect, the present invention provides a method of altering or restoring pigmentation in mammalian skin, hair, wool or fur, which comprises administering to a mammal an effective amount of a compound which alters cellular production of nitric oxide, wherein an increase in nitric oxide production results in increased pigmentation, and a decrease in nitric oxide production results in decreased pigmentation.
In yet another aspect, the present invention provides a method of altering pigmentation in mammalian skin, hair, wool or fur, which comprises administering to a mammal an effective amount of a compound which alters cellular production of cyclic guanosine monophosphate, wherein an increase in cyclic guanosine monophosphate production results in increased pigmentation, and a decrease in cyclic guanosine monophosphate production results in decreased pigmentation.
In yet another aspect, the present invention provides a method of altering pigmentation in mammalian skin, hair, wool or fur, which comprises administering to a mammal an effective amount of a compound which alters cellular activity of protein kinase G, wherein an increase in protein kinase G activity results in increased pigmentation, and a decrease in protein kinase G activity results in decreased pigmentation.
In yet another aspect, the present invention provides a method of identifying a substance which alters pigmentation in mammalian melanocytes, which comprises evaluating the effect the substance has on cellular production of nitric oxide, wherein if such production is altered, then the pigmentation in mammalian melanocytes is altered.
In yet another aspect, the present invention provides a method of identifying a substance which alters pigmentation in mammalian melanocytes, which comprises evaluating the effect the substance has on cellular production of cyclic guanosine monophosphate, wherein if such production is altered, then the pigmentation in mammalian epidermal melanocytes is altered.
In yet another aspect, the present invention provides a method of identifying a substance which alters pigmentation in mammalian melanocytes, which comprises evaluating the effect the substance has on cellular activity of protein kinase G, wherein if such activity is altered, then the pigmentation in mammalian epidermal melanocytes is altered.